Carboxamide compounds and uses thereof

Abstract

Disclosed are compounds of Formula (I′) methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

What is claimed is: 
     
       1. A method for treating a cancer in a patient, said method comprising: administering to the patient a therapeutically effective amount of a compound selected from:
 N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide; 
 N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide; and 
 N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, 
 or a pharmaceutically acceptable salt of any of the aforementioned; 
 wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, pancreatic cancer, Burkitt's lymphoma, acute promonocytic leukemia, and hepatocellular carcinoma. 
 
     
     
       2. The method of  claim 1 , wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer. 
     
     
       3. The method of  claim 1 , wherein the cancer is breast cancer. 
     
     
       4. The method of  claim 1 , wherein the cancer is colorectal cancer. 
     
     
       5. The method of  claim 1 , wherein the cancer is lung cancer. 
     
     
       6. The method of  claim 1 , wherein the cancer is ovarian cancer. 
     
     
       7. The method of  claim 1 , wherein the cancer is pancreatic cancer. 
     
     
       8. The method of  claim 1 , wherein the cancer is Burkitt's lymphoma. 
     
     
       9. The method of  claim 1 , wherein the cancer is acute promonocytic leukemia. 
     
     
       10. The method of  claim 1 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       11. The method of  claim 1 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide. 
     
     
       12. The method of  claim 2 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       13. The method of  claim 8 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       14. The method of  claim 9 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       15. The method of  claim 1 , wherein the compound is N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       16. The method of  claim 1 , wherein the compound is N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide. 
     
     
       17. The method of  claim 2 , wherein the compound is N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       18. The method of  claim 8 , wherein the compound is N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       19. The method of  claim 9 , wherein the compound is N-(2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       20. The method of  claim 1 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       21. The method of  claim 1 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide. 
     
     
       22. The method of  claim 2 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       23. The method of  claim 8 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       24. The method of  claim 9 , wherein the compound is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
       25. The method of  claim 1 , wherein the cancer is hepatocellular carcinoma.